8 The discovery of miRNAs is one of the major developments in molecular biology during the last decade which has added another dimension to study the regulation of gene expression. miRNA gene transcription takes place within the nucleus, following the cleavage of the ∼80 nucleotide stem-loop pri-microRNA precursor performed by the microprocessor complex consisting of Drosha, an RNaseIII-type nuclease and a double-strand

RNA-binding protein co-factor, DGCR8 (DiGeorge syndrome critical region 8 gene) in humans. The parturient pri-miRNAs are processed Alectinib into 60–70 nucleotide hairpin structure (pre-miRNAs) and are exported from the nucleus to the cytoplasm supported by nucleocytoplasmic shuttle protein Exportin-5 in a Ran-GTP dependent manner. Pre-miRNAs are further cleaved, into an asymmetric duplex by the action of Dicer and accessory proteins Transactivation-responsive RNA-binding protein (TRBP) and PACT in humans, to remove the loop sequence by forming a short-lived asymmetric duplex intermediate (miRNA: miRNA), with a duplex about 22 nucleotides in length. This precursor is cleaved to generate ∼21–25-nucleotide mature miRNAs (Fig. 1). The mature miRNA is loaded into

the microRNA-induced silencing complex (miRISC), which binds to target mRNA resulting in either degradation of mRNA, to blockage of translation http://www.selleckchem.com/products/ABT-263.html without mRNA degradation.9 and 10 To date, approximately 1000 different mature miRNAs have been reported in humans. A single miRNA may control hundreds of target mRNAs and hundreds of miRNA genes are predicted, these influences may have consequential effects on gene expression networks.1 For majority of individual miRNAs the

function remains unknown. Particular miRNAs are frequently expressed enough only in specific cell types or in developmental stages. Number of miRNAs have been identified in a wide range of species in plants, nematodes, fruit flies, viruses and human.11 No miRNAs have been found in yeast and bacteria. Recent studies have also provided evidence that abnormal expression of specific miRNAs is implicated in a number of human diseases, including cancer.12 In recent years there has also been an explosion of research reports on miRNA myriad role in biomedical fields, as master regulators of the human genome.13 miRNA deficiencies or, abundances due to the single point mutation or epigenetic silencing, of the abnormal expression level have been correlated with a number of clinically important patho physiology of diseases and their status, to become important diagnostic and prognostic tools.14 They play crucial roles in a wide range of tools of medicine for prevention, diagnosis, prognosis and therapy of human diseases. miRNA expression can be appropriately linked to a variety of diseases including cancer.